Current research is focused on a chronic-relapsing model of experimental allergic encephalomyelitis (EAE). This disease is produced by the transfer of lymphocytes sensitized against MBP to syngeneic mice. The neurologic dysfunction is characterized pathologically by inflammation and primary demyelination. The immunological mechanisms responsible for the initial episode and the chronic disease are being investigated. Because the migration of immune cells from the blood into the central nervous system (CNS) occurs before clinical disease, interactions between endothelial cells (EC) which form the blood-brain barrier (BBB) and immune cells are being studied in vitro. The function of various adhesion molecules in both adherence and lymphocyte signaling are being examined. The effects of various cytokines on lymphocyte/EC interactions and on clinical disease are being studied. Astrocytes and microglia are in close proximity to EC, and in this anatomical location, may react with immune cells. The expression of major histocompatibility complex (MHC) molecules in these cells and the influence of cytokines on the regulation of these molecules is being evaluated using cultures of murine fetal CNS cells, adult human glia cells, and murine brain capillary EC. Expression and regulation of MHC molecules by neurons is also being examined in human neuroblastoma cell lines. The administration of transforming growth factor-beta1 (TGF-beta1) prior to the onset of disease, reduces the intensity of the initial episode. When given after the first episode, the subsequent course is significantly less severe. TGF-beta1 has been demonstrated by immunochemical techniques in EAE lesions which suggests that this cytokine has a regulatory function in vivo. The administration of interferon-gamma (IFN-gamma), also inhibits the initial episode and it is possible that this cytokine increases the endogenous expression of TGF-beta1.